1. Field of the Invention
The chemical processes of the present invention produce antibacterial agents of the class commonly called cephalosporins or intermediates for said production.
2. Description of the Prior Art
The patent literature alone contains a large number of disclosures of the production of cephalosporins by the reaction with a silylated nucleus [such as 7-aminocephalosporanic acid (7-ACA) or 7-aminodesacetoxycephalosporanic acid] of a sidechain acid in the form of its acid chloride. When that acid contains a free amino group such group is preferably blocked, as by protonation, and so use is made, for example, of 2-phenylglycylchloride hydrochloride to make cephalexin. The 4-carboxyl group of the nucleus may be blocked by silylation or by esterification. Some examples of such patents are U.S. Pat. Nos. 3,671,449, 3,694,437, 3,741,959, 3,957,773, 3,965,098, 4,051,131 and U.K. Pat. No. 1,073,530. In many instances the 3-acetoxy group of 7-ACA has been displaced before acylation by a heterocyclic thiol, e.g. ceforanide (U.S. Pat. No. 4,100,346 and see the description of prior art therein), cefatrizine (U.S. Pat. No. 3,867,380), cefaparole (U.S. Pat. No. 3,641,021), cefazolin (U.S. Pat. Nos. 3,516,997 and 3,819,623), cefazaflur (U.S. Pat. No. 3,828,037) and the like or by other types of thiols as reviewed in U.S. Pat. No. 3,928,336.
A search of Chemical Abstracts Formula Indexes Vols. 58087 showed that I had not been indexed. ##STR1##
Siloxycarbonylamino derivatives are indexed under silanol, carbamic acid and under N-carboxy derivatives of compounds as the trimethylsilyl ester.
However, the following papers appear of some interest:
1. Breederveld, H.: The interaction of dialkylaminosilanes with carbon disulphide. A novel reaction in organosilicon chemistry. Recueil, 79, 1126 (1960).
2. Cragg, R. H.; Lappert, M. F.: Amino-derivatives of metals and metalloids. Part IV. Aminosilylation and aminophosphination of some unsatured substrates. J. Chem. Soc. (A), 82-85 (1966).
3. Kricheldorf, H. R.: Herstellung von N-Silyloxycarbonylaminosaure-derivaten. Synthesis, 259-60 (1970) (Ger.): C.A. 73, 45820r (1970). 4. Kricheldorf, H. R.: The preparation of amino acid N-carboxyanhydrides (NCAs) from N-siloxycarbonyl amino acid trimethylsilyl esters. Chem. Ber., 104, 87-91 (1971) (Ger.); C.A. 74, 54156b (1971).
5. Mironov, V. F.; Kozyukov, V. P.; Kirilin, A. D., et al.: Synthesis and reactions of silyl carbamates. New method for the preparation of organic isocyanates without the use of phosgene. Zh Obshch Khim, 45, 1971-1973 (1975).
6. Sheludyakov, V. D.; Kirilin, A. D.; Mironov, V. F.: New method for the preparation of (carbamoyloxy)-silanes. Zh Obshch Khim, 45, 471 (1975).
7. Mironov, V. F.; Sheludyakov, V. D.; Kirilin, A. D.: Siloxycarbonylation of amines. Zh Obshch Khim, 46, 2297-98 (1976).
8. Farbenfabriken Bayer A-G (Oertel, G., et al.): Organosilicon compounds. Chem. Abs., 60, 6868b. (Ger. Offen. 1,157,226).